The objective of this study is to identify and characterize baculovirus genes that control host specificity. This will contribute to determining the genetic basis of host and tissue tropisms in baculoviruses. The long term goal is to develop improved methods for controlling insect pests. Baculoviruses, invertebrate specific pathogens that infect a wide range of insects, including disease vectors, are an attractive alternative to chemical insecticides. Because of increased resistance to chemical insecticides and the development of drug resistant parasites, new strategies for controlling vector insects are needed. Restricted host and tissue tropisms exhibited by baculoviruses limit their usefulness as insecticides. For example, baculoviruses observed in mosquitoes are seen only in midgut tissues. Autographa californica nuclear polyhedrosis (AcMNPV), a baculovirus with an unusually broad host range, serves as a model system for studying the molecular biology of baculoviruses. To address the problem of host and tissue specificity experimentally, a genetic approach will be used. Genes that contribute to the broad host range observed in AcMNPV will be identified by mutating AcMNPV and isolating mutants that have reduced host range in tissue culture. After initial characterization of the mutants, the mutated genes will he molecularly cloned and sequenced. Additional experiments to determine the normal function of the mutated genes in baculovirus infections will be designed and executed. These experiments will be determined by observations of the mutant phenotypes and predictions of possible function, based on analysis of the protein and DNA sequences. These studies will contribute towards improved insect control in two ways. First, improved viral insecticides could be developed for specific insects. Second, because viruses reflect the normal functions of their hosts, the mechanisms used by the virus to control host range might suggest additional novel approaches for insect control.